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Are the Results of Randomized Controlled Trials on Anticoagulation in Patients With Atrial Fibrillation Generalizable to Clinical Practice?
Andrew Evans, MRCP;
Lalit Kalra, PhD, FRCP
Arch Intern Med. 2001;161:1443-1447.
ABSTRACT
| |
Background Randomized trials demonstrate a clear benefit of anticoagulation in
patients with atrial fibrillation at risk of stroke, but the proportion of
eligible patients who are treated with anticoagulants remains low. The reluctance
to treat all eligible patients with anticoagulants may be due to studies in
clinical practice showing variable risk-benefit, raising concerns about application
to general medical practice.
Methods A systematic review of published medical literature was performed to
identify studies of patients with atrial fibrillation who were treated with
warfarin in actual clinical practice. Data from these studies were compared
with pooled data from randomized controlled trials.
Results Three studies met the predefined criteria, each in a different health
care setting, totaling 410 patients with 842 patient-years of follow-up. Patients
in clinical practice were older and had more comorbid conditions compared
with trial participants. However, the ischemic stroke rate was similar between
clinical practice and randomized studies (1.8% [95% confidence interval {CI},
0.9%-2.7%] vs 1.4% [95% CI, 0.9%-2.0%]). Intracranial hemorrhage (0.1% [95%
CI, 0%-0.3%] vs 0.3% [95% CI, 0.06%-0.5%]) and major bleeding (1.1% [95% CI,
0.4%-1.8%] vs 1.3% [95% CI, 0.8%-1.8%]) rates were also similar. There was
a higher rate of minor bleeding in clinical practice than in trials (12.0%
[95% CI, 9.7%-14.3%] vs 7.9% [95% CI, 6.6%-9.2%]).
Conclusions Patients who undergo anticoagulation for atrial fibrillation in actual
clinical practice differ from those in randomized trials, but have similar
rates of stroke and major bleeding. The risk of minor bleeding is higher and
may require more intensive monitoring in practice.
INTRODUCTION
STROKE IS THE third most common cause of death and the most common cause
of severe adult disability.1 Atrial fibrillation
increases the risk of stroke 6-fold, and 20% to 30% of acute ischemic strokes
are cardioembolic in origin.2-3
These strokes tend to be more severe and are associated with poorer outcomes.4
Randomized trials5-11
have clearly demonstrated the effectiveness of anticoagulation in preventing
stroke in patients with atrial fibrillation, and expert panels12
recommend that all patients with atrial fibrillation at high stroke risk should
be considered for anticoagulation. Clinical guidelines, which will identify
those at high risk, have also been developed.13-14
However, studies14-16
of clinical practice consistently report that only a quarter to half of eligible
patients with atrial fibrillation undergo anticoagulation.
One of the major reasons for this underprescribing is the concern that
the benefits of warfarin therapy were demonstrated in highly selected patients
with optimal anticoagulation control and will not be reproduced in actual
practice.17 This was supported by an early
report18 that showed that the quality of anticoagulation,
the therapeutic efficacy of warfarin, and the low complication rates seen
in randomized trials were not matched in clinical practice. This conflicts
with a more recent study19 that showed that
the stroke rate and the risk of major hemorrhage in clinical practice was
comparable to that seen in randomized trials for patients with atrial fibrillation
undergoing anticoagulation for stroke prevention, despite these patients being
older than those included in randomized studies. The limitations of both of
these studies were that they were undertaken in single district cohorts with
uniform anticoagulation practices and within a single health care system.
It is not known whether their findings will be generalizable to other settings
with different patient groups, different anticoagulation practices, or different
health care systems.
The ultimate objective of anticoagulation for atrial fibrillation is
to reduce the incidence of stroke in "real-life" conditions. Routine clinical
settings have a high proportion of patients who would not meet strict inclusion
criteria and may not be as compliant with interventions as those included
in randomized studies. The interventions are delivered by staff or services
that may not perform as well as those in trials. Widespread implementation
of anticoagulation will have greater support in actual practice if experience
in a range of clinical settings continues to show a benefit with anticoagulation.
In view of this, a literature review was undertaken to identify nonrandomized
clinical studies on anticoagulation in patients with atrial fibrillation,
which were analyzed in the context of randomized trials to determine if trial
efficacy translated into clinical effectiveness.
MATERIALS AND METHODS
A systematic review of the medical literature was performed using Ovid
MEDLINE, PubMed, and the Cochrane database searching for keywords ("atrial
fibrillation," "anticoagulation," and "warfarin"), text words ("clinical,"
"actual," or "mainstream practice"), or a combination of these words. Titles
and abstracts were screened for studies of anticoagulation in patients with
atrial fibrillation for primary stroke prevention in actual or clinical practice
(outside of a controlled trial). The criteria for inclusion were as follows:
- A prospective cohort or retrospective case note
review in which all dropouts had been identified and measures undertaken to
minimize nonreport bias. These included enumeration of all eligible patients
(and not only those undergoing anticoagulation), changes in treatment, and
reasons for failure to reach specified end points.
- Patients recruited from mainstream clinical practice
settings based on stroke risk and the risk of hemorrhage, unrestricted by
age, sex, location, or other nonclinical considerations.
- Anticoagulation undertaken within routine settings
using local guidelines and delivered by nonresearch staff.
- Longitudinal data on stroke rate and
hemorrhagic complications.
Thirty-two articles were retrieved for more detailed analysis. The references
of these articles were scanned to identify other articles with similar characteristics,
which may have been missed in database searches. Articles were assessed independently
by each of us for various variables, including type of study, patient numbers,
demographics, warfarin exposure, mortality, stroke incidence, bleeding complications,
and anticoagulation control. We agreed on the inclusion of 6 articles,18-23
which gave information on at least 7 of the variables previously mentioned
for further joint review. Following the review, 2 studies21-22
were excluded because they reported results from all patients undergoing anticoagulation
(those with deep vein thromboses, pulmonary embolism, and prosthetic valves)
and it was not possible to obtain data on the subgroup with atrial fibrillation
alone. One study23 (a retrospective study of
elderly nursing home residents) was not included in the analyses, because
all patients were in institutional care and were not representative of mainstream
practice. Only 3 studies18-20
met all the predefined criteria for inclusion in the review.
Comparisons were made between individual studies and pooled data from
these studies with combined data from randomized controlled trials.11 Two-sample confidence intervals (CIs) for the difference
of means and proportions were used to compare important prognostic variables
between randomized trials and the present sample. The event rate per 100 patient-years
was calculated, and the exact Poisson CIs were used for comparisons of clinical
outcomes. A Cox proportional hazards analysis was used to adjust for differences
in patient characteristics. Despite the study on institutionalized patients
not meeting predefined criteria, a second analysis of pooled data that included
the results of this study was undertaken to evaluate if such inclusion significantly
affected the results of the main analysis.
RESULTS
Three studies18-20
(one each from the United States, Canada, and England) met the predefined
criteria for inclusion. These studies had similar definitions for atrial fibrillation,
risk stratification, and criteria for anticoagulation. The definitions of
end points (ischemic stroke) and of major and minor hemorrhages were similar
among the 3 studies. Tests of homogeneity were applied and did not show significant
(P>.05 for all) differences in outcome variables.
In the US study,18 anticoagulation was
undertaken in 156 (66%) of 238 patients with atrial fibrillation in a health
maintenance organization. Of the 82 patients (34%) not undergoing anticoagulation,
40 had contraindications to warfarin use, 12 refused treatment, and 30 were
not offered anticoagulation for unspecified reasons. The English study19 was undertaken in a district hospital and included
167 (49%) of the 344 patients with atrial fibrillation from outpatient settings.
Of the 177 patients excluded, 76 were taking warfarin before the study, 38
had contraindications to anticoagulation, 5 refused treatment, and 58 were
not offered anticoagulation because of a low stroke risk. In the Canadian
study,20 undertaken in a teaching and a community
hospital, 87 (39%) of 221 patients took warfarin for the duration of the study.
Reasons for exclusion from anticoagulation were not available.
Patients in the English study were significantly older than those included
in the US (age difference, 8 years; P = .01) and
the Canadian (age difference, 6 years; P = .02) studies
(Table 1). There was also a significantly
(P = .001) higher proportion of women included in
the English study compared with the other 2 studies. Patients included in
all 3 studies had high levels of comorbidity. Pooled data from clinical studies
showed that patients in actual practice were, on average, 6 years older and
consisted of a higher proportion of women compared with patients included
in randomized trials (Table 1).
A significantly (P = .001) higher proportion of patients
in the clinical sample had previous cerebrovascular disease.
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Table 1. Patient Characteristics of Studies in Clinical Practice and
Pooled Clinical and Trial Data*
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Although the target international normalized ratio was similar in all
studies,24 anticoagulation was managed differently.
In the United States, long-term anticoagulation was managed by the patient's
primary care internist, whereas in England, this was undertaken in a general
anticoagulation clinic run by the hematology department. Patients in the Canadian
study underwent anticoagulation by individual physicians (internists, general
practitioners, cardiologists, or hematologists) according to their own practice
(J. Caro, MD, written communication, 2000). In clinical trials, patients'
international normalized ratios were in the target range on 68% of days, which
was significantly more than achieved in clinical practice (P<.001). There was also a significant difference in days spent in
the target range between the US and the English studies (50% vs 61% of days; P<.01). The international normalized ratios were higher
than the desired range for 30% of the days in the US (P<.001) and 13% of the days in the English studies compared with
8% of the days in clinical trials. There were no differences in the proportion
of days spent below the target range among randomized trials and clinical
studies.
The annual event rate for ischemic stroke for patients undergoing anticoagulation
was similar among the 3 studies and varied between 1.6% and 2.0% (Table 2). The annual stroke rate of individual
studies and of pooled data from these studies compared favorably with that
of patients who underwent anticoagulation in the pooled analysis of randomized
trials. Only 1 of 410 patients who underwent anticoagulation in actual practice
had an intracranial hemorrhage, and major bleeding was seen in only 10 patients
(Table 2). The annual event rate
for major bleeding in the clinical studies was also not different from that
seen in the combined data from randomized trials. The annual rate of minor
bleeding in clinical practice was significantly (P
= .002) higher than in randomized studies.
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Table 2. Event Numbers and Rates in Studies and Combined Clinical and
Combined Trial Data*
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Data from the study on institutionalized patients23
were combined with the pooled data from the other 3 studies18-20
to evaluate whether this inclusion significantly changed the results. This
study23 showed a stroke rate of 2.1% (95% CI,
0.1%-4.1%), and the major bleeding rate (with a broader definition of major
bleeding) was 5.9% (95% CI, 2.0%-7.9%). These rates, combined with the pooled
data of the actual clinical practice group, showed a stroke rate of 1.8% (95%
CI, 1.0%-2.6%; P = .4) and a major hemorrhage rate
of 2.1% (95% CI, 1.5%-2.7%; P = .14), which also
were not significantly different from the pooled randomized controlled trial
data.
COMMENT
Despite the diversity of settings and anticoagulation practices, there
were no significant differences in the annual ischemic stroke rate or major
bleeding rate in patients undergoing anticoagulation between studies in actual
clinical practice. Although patients in clinical practice were significantly
older and had higher levels of comorbidity, the annual stroke and major hemorrhage
rates for individual studies and for combined data from all clinical practice
studies were comparable to those seen in randomized studies. These findings
show that anticoagulation in patients with atrial fibrillation is effective
and safe in general medical practice in different settings.
The present study suggests that anticoagulation control in actual clinical
practice is likely to be poorer than achieved in clinical trials. Several
risk factors for poor anticoagulation control have been suggested; they can
be clinical (eg, intercurrent illness or use of other drugs), psychological
(eg, mood or compliance),25 or environmental
(access to and differences between anticoagulation services).26
These factors need to be addressed when planning services. The poorer anticoagulation
control did not translate into less effective prevention of stroke, probably
because there were no significant differences between the time spent below
the target range between actual practice and randomized studies. However,
there was a significant increase in the number of minor hemorrhages in actual
practice, especially in studies in which patients spent a longer time above
the target range. This increase may have important implications for patients'
perceptions of health and benefit from treatment, which would affect compliance.27 It also has important implications for the costs
of care in terms of service use by patients with these complications and the
need for increased monitoring to prevent such episodes.
Strictly speaking, the method of meta-analysis can only be applied to
randomized controlled studies.28-29
Although there are inherent problems in combining observational data from
nonidentical sources, the pooling of results from several different sources
can be invaluable in overcoming the potential lack of generalizability of
small studies in single settings. The pooling of data from several similar
observational studies may also increase the power of analysis, ensuring that
important differences between actual practice and randomized trials are not
obscured by large CIs in small studies. There were no significant differences
on homogeneity testing among the studies included in this analysis. The pooling
of data resulted in the narrowing of CIs for events to the level at which
they were nearly identical to those for pooled data from randomized studies,
giving further support to the findings of individual studies.
Although pooled data analyses provide a broad overview of existing evidence,
they have their own limitations.29 These analyses
are heavily dependent on published data, and a bias due to nonpublication
of negative results cannot be prevented.30
Although statistical methods to detect possible publication bias exist,31 these would not be meaningful with the few studies
available for this analysis. Differences in the method of data collection
or analysis may be another source of bias. The case note review undertaken
by Gottlieb and Salem-Schatz18 is likely to
lead to an underestimation of fatal events (or complications), as only patients
alive at the time of the study were included. The exclusion from analysis
of patients who withdrew from warfarin therapy before reaching a study end
point20 can result in underestimation of minor
adverse events. The use of "intention-to-treat" rather than "on treatment"
analysis19 may underestimate the benefit of
anticoagulation. There were differences between groups in age, sex, and comorbidity
among studies (Table 1), which
reflect differences in the populations in which these studies were undertaken.
For example, the US study18 was undertaken
in a health maintenance organization that is likely to include younger patients
than the English study,19 which was undertaken
in an area with a higher than average proportion of older people. Despite
the variability between the populations and limitations in methods, the comparability
of outcomes in clinical settings reinforces the central message that anticoagulation
can be safe and effective in a range of mainstream settings.
There is a risk that adoption of practice recommendations based on results
of controlled clinical trials may fail to yield optimal results in clinical
practice. This is because randomized controlled studies tend to focus on single
defined interventions, and other variables are controlled. Clinical practice,
on the other hand, is complex and consists of various connected components,
which need to be taken into account.32 These
include not only the treatment in question or the patients requiring such
treatment but the whole spectrum of how the treatment is provided and the
environmental constraints of the setting in which it is provided. This overview
of studies in actual practice shows that research-based knowledge can be synthesized
with real-life factors to provide an effective system for preventing stroke
in patients with atrial fibrillation in a wide range of patients treated in
diverse clinical settings.
AUTHOR INFORMATION
Accepted for publication November 1, 2000.
Corresponding author: Andrew Evans, MRCP, Department of Diabetes,
Endocrinology, and Internal Medicine, Guy's, King's and St Thomas' School
of Medicine, Denmark Hill Campus, Bessemer Road, London SE5 8PJ, England
(e-mail: andy.evans{at}kcl.ac.uk).
From the Department of Diabetes, Endocrinology, and Internal Medicine,
Guy's, King's and St Thomas' School of Medicine, King's College, London, England.
REFERENCES
| |
1. Kalache A, Aboderin I. Stroke: the global burden. Health Policy Plan. 1995;10:1-21.
FREE FULL TEXT
2. Broderick JP, Philip SJ, O'Fallon M, Frye RL, Wishant JP. Relationship of cardiac disease to stroke occurrence. Stroke. 1992;23:1250-1256.
FREE FULL TEXT
3. Hart RG, Halperin JL. Atrial fibrillation and thromboembolism: a decade of progress in stroke
prevention. Ann Intern Med. 1999;131:688-695.
FREE FULL TEXT
4. Jorgensen HS, Nakayama H, Reith J, Raaschou HO, Olsen TS. Acute stroke with atrial fibrillation: the Copenhagen Stroke Study. Stroke. 1996;27:1765-1769.
FREE FULL TEXT
5. Peterson P, Boyson G, Godtfredsen J, Andersen ED, Andersen B for the Copenhagen Atrial Fibrillation Aspirin Anticoagulation Study
Group. Placebo-controlled randomised trial of warfarin and aspirin for prevention
of thromboembolic complications in chronic atrial fibrillation. Lancet. 1989;1:175-189.
ISI
| PUBMED
6. Boston Area Anticoagulation Trial for Atrial Fibrillation (BAATAF)
Investigators. The effect of low-dose warfarin on the risk of stroke in patients with
nonrheumatic atrial fibrillation. N Engl J Med. 1990;323:1505-1511.
ABSTRACT
7. Stroke Prevention in Atrial Fibrillation (SPAF) Investigators. Stroke Prevention in Atrial Fibrillation Study: final results. Circulation. 1991;84:527-539.
FREE FULL TEXT
8. Connolly SJ, Laupacis A, Gent M, Roberts RS, Cairns JA, Joyner C. Canadian Atrial Fibrillation Anticoagulation (CAFA) Study. J Am Coll Cardiol. 1991;18:349-355.
ABSTRACT
9. Ezekowitz MD, Bridgers SL, James KE, et al. Warfarin in the prevention of stroke associated with non-rheumatic
atrial fibrillation (SPINAF). N Engl J Med. 1992;327:1406-1412.
ABSTRACT
10. SPAF Investigators. Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus
aspirin for high-risk patients with atrial fibrillation. Lancet. 1996;348:633-638.
FULL TEXT
|
ISI
| PUBMED
11. Atrial Fibrillation Investigators. Risk factors for stroke and efficacy of antithrombotic treatment in
atrial fibrillation: analysis of pooled data from five randomized controlled
studies. Arch Intern Med. 1994;154:1449-1457.
FREE FULL TEXT
12. Laupacis A, Albers G, Dalen J, Dunn MI, Jacobson AK, Singer DE. Antithrombotic therapy in atrial fibrillation. Chest. 1998;114(suppl):579S-589S.
13. Thomson R, Parkin D, Eccles M, Sudlow M, Robinson A. Decision analysis and guidelines for anticoagulant therapy to prevent
stroke in patients with atrial fibrillation. Lancet. 2000;355:956-962.
FULL TEXT
|
ISI
| PUBMED
14. Stafford RS, Singer DE. National patterns of warfarin use in atrial fibrillation. Arch Intern Med. 1996;156:2537-2541.
FREE FULL TEXT
15. Albers GW, Yim JM, Belew KM, et al. Status of antithrombotic therapy for patients with atrial fibrillation
in university hospitals. Arch Intern Med. 1996;156:2311-2316.
FREE FULL TEXT
16. Sudlow M, Thomson R, Thwaites B, Rodgers H, Kenny RA. Prevalence of atrial fibrillation and eligibility for anticoagulants
in the community. Lancet. 1998;352:1167-1171.
FULL TEXT
|
ISI
| PUBMED
17. Hardman SMC, Cowie M. Anticoagulation in heart disease. BMJ. 1999;318:238-244.
FREE FULL TEXT
18. Gottlieb LK, Salem-Schatz S. Anticoagulation in atrial fibrillation: does efficacy in clinical trials
translate into effectiveness in practice? Arch Intern Med. 1994;154:1945-1953.
FREE FULL TEXT
19. Kalra L, Yu G, Perez I, Lakhani A, Donaldson N. Prospective cohort study to determine if trial efficacy of anticoagulation
for stroke prevention in atrial fibrillation translates into clinical effectiveness. BMJ. 2000;320:1236-1239.
FREE FULL TEXT
20. Caro JJ, Flegel KM, Orejuela ME, Kelley HE, Speckman JL, Migliaccio-Walle K. Anticoagulant prophylaxis against stroke in atrial fibrillation: effectiveness
in actual practice. CMAJ. 1999;161:493-497.
FREE FULL TEXT
21. Gitter MJ, Jaeger TM, Petterson TM, Gersh BJ, Silverstein MD. Bleeding and thromboembolism during anticoagulant therapy: a population-based
study in Rochester, Minnesota. Mayo Clin Proc. 1995;70:725-733.
ABSTRACT
22. Fihn SD, Callahan CM, Martin DC, McDonell MB, Henikoff JG, White RH. The risk and severity of bleeding complications in elderly patients
treated with warfarin: the National Consortium of Anticoagulant Clinics. Ann Intern Med. 1996;124:970-979.
FREE FULL TEXT
23. Goldenberg GM, Silverstone FA, Rangu S, Leventer SL. Outcomes of long-term anticoagulation in frail elderly patients with
atrial fibrillation. Clin Drug Invest. 1999;17:483-488.
FULL TEXT
24. The European Atrial Fibrillation Study Group. Optimal oral anticoagulant therapy in patients with nonrheumatic atrial
fibrillation and recent cerebral ischaemia. N Engl J Med. 1995;333:54-55.
FREE FULL TEXT
25. Hylek EM, Heiman H, Skates SJ, Sheehan MA, Singer DE. Acetaminophen and other risk factors for excessive warfarin anticoagulation. JAMA. 1998;279:657-662.
FREE FULL TEXT
26. Pell JP, McIver B, Stuart P, Malone DN, Alcock J. Comparison of anticoagulant control among patients attending general
practice and a hospital anticoagulant clinic. Br J Gen Pract. 1993;43:152-154.
ISI
| PUBMED
27. Howitt A, Armstrong D. Implementing evidence based medicine in general practice: audit and
qualitative study of antithrombotic treatment for atrial fibrillation. BMJ. 1999;318:1324-1327.
FREE FULL TEXT
28. Kunz R, Oxman D. The unpredictability paradox: review of empirical comparisons of randomised
and non-randomised clinical trials. BMJ. 1998;317:1185-1190.
FREE FULL TEXT
29. McKee M, Britton A, Black N, McPherson K, Sanderson C, Bain C. Methods in health services research: interpreting the evidence: choosing
between randomised and non-randomised studies. BMJ. 1999;319:312-315.
FREE FULL TEXT
30. Stern JM, Simes RJ. Publication bias: evidence of delayed publication in a cohort study
of clinical research projects. BMJ. 1997;315:640-645.
FREE FULL TEXT
31. Begg CB. Publication bias. In: Cooper H, Hedges LV, eds. The Handbook of Research
Synthesis. New York, NY: Russell Sage Foundation; 1994:399-409.
32. Checkland P. Systems Thinking, Systems Practice. New York, NY: John Wiley & Sons Inc; 1993.
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